Environmental electrophiles such as 1,4-napthoquinone (1,4-NQ) and methylmercury easily bind to the protein thiols, thereby inducing cytotoxicity. In this study, we investigated the cytoprotective roles of reactive sulfur species, a highly nucleophilic compounds. We found that exposure of primary mouse hepatocytes to polysulfide and 1,4-NQ markedly decreased 1,4-NQ-mediated cell death and S-arylation of cellular proteins. Activation of cell survival signaling under exposure to 1,4-NQ was suppressed in the presence of polysulfides. These results suggest that reactive sulfur species act as a initial cytoprotective factor by capturing this electrophile.